Measles and rubella seroprevalence in a population of young adult blood donors, France 2013.

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18-32 years old. A secondary objective was to estimate measles incidence in this population during the 2009-2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18-32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18-32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009-2011. Applying our results to French census data would suggest that around 1 million people aged 18-32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings.

Transfusion-transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource-constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high-income countries, primarily given the high costs of use. Logistical considerations, particularly in low-resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.

Collapsing glomerulopathy associated lupus in a black female with homozygous APOL1 mutation.

Collapsing glomerulopathy (CG), characterized by collapse of the glomerular capillary loops onto the mesangial stalks is rarely associated to systemic lupus erythematosus (SLE). Recently a genetic predisposition to HIV associated nephropathy (HIVAN) has been shown in Afro-Americans: MYH9 polymorhism in 2008 and then APOL1 variants (G1 and G2 alleles) in 2010 were shown to be strongly associated with HIVAN. We describe here for the first time the association of CG in a young Afro-American female with SLE having a homozygous mutation of APOL1. The clinical history, laboratory findings and immunofluorescence all confirmed a diagnosis of SLE. However, studies for factors associated with collapsing glomerulopathy in other situations were consistently negative. As this Afro-American patient developed a CG, we performed genotyping of APOL1. It was found that she is homozygotic for the G2 allele of APOL1. Despite.

Evaluation of the hemostatic potential including thrombin generation of three different therapeutic pathogen-reduced plasmas.

BACKGROUND AND OBJECTIVES: Several pathogen inactivation methods currently applied to therapeutic plasma may result in products with different hemostatic properties. This study aims at evaluating and comparing the hemostatic potential of different therapeutic plasma preparations currently available in France. MATERIALS AND METHODS: We studied three types of pathogen-reduced plasma for transfusion (MB/light, Amotosalen/UVA, industrial S/D plasma). Quarantine, non-pathogen-reduced plasma, was used as a control. This study compared more specifically the content in FVIII, fibrinogen (clottable and antigen assays) and ADAMTS-13 and evaluated the intrinsic hemostatic properties using a thrombin generation test [Calibrated Automated Thrombogram (CAT)] at high and low concentrations of tissue factor to assess the maximum quantity of thrombin generated or the contribution of FVIII and FIX in the amplification phase of thrombin generation, respectively. RESULTS: The median FVIII concentration was >70 IU/dl for each preparation. Endogenous thrombin potential values were significantly different among the methods of plasma preparation (P<0·001) but were all in the range of the values measured in donors' plasma. Control by the thrombomodulin-activated protein C system was preserved in all preparations (>50% inhibition of endogenous thrombin potential). Fibrinogen concentrations were all within normal range but fibrinogen levels were lower in the plasmas treated with photochemical methods. ADAMTS-13 levels were preserved. CONCLUSION: The hemostatic potential appears well preserved in all therapeutic plasmas tested but there are some differences between preparations, the clinical relevance of which remains to be elucidated.

[Lights on connections between humanitarian medicine and general medicine]. / Réflexions sur certains aspects de la médecine générale à partir de constats sur l'humanitaire.

Humanitarian Medicine's practical experiences show the potential violence of the medicine's power over bodies everywhere. The inequality between assistance and people receiving benefits is comparable to the asymmetrical relationship between doctor and patient. Efforts have to be done in order to comprehend other possibilities of life's organization. The understanding of double subjectivities in the therapeutic relationship is a requirement for success, in any situation--as usual. Furthermore, the adverse effects of assistance remind us the primary principle not to harm. These admissions of failure urge to develop assessment reasoning, including all factors of influence on health (resources, policy...), and an approach which aims people to become self-sufficient.

Renal histopathological lesions after lung transplantation in patients with cystic fibrosis.

We have analyzed the evolution of renal status beyond the perioperative period in patients with cystic fibrosis (CF) undergoing lung transplantation and presented histological analysis of 15 patients biopsied for an episode of accelerated renal function loss (RFL). Episodes of accelerated RFL after the perioperative period occurred in 32.5% of patients and significantly raised the risk of end-stage renal disease (ESRD) (p < 0.001). The histologic lesions associated with these episodes differed according to the time of onset. Early onset (10 cases) was associated with tubulointerstitial lesions in the form of oxalate nephropathy (50%) and/or a pigmented tubulopathy (80%). This latter was correlated with treatment with antiviral agents (p = 0.002) and aminoside and glycopeptide antibiotics (p = 0.03) administered in the month preceding biopsy. Lesions in late episodes of accelerated RFL (5 cases) were principally vascular: arteriosclerosis and arteriolosclerosis (p = 0.007, p = 0.00002), correlated with diabetic glomerulosclerosis or focal segmental glomerulosclerosis in the absence of prominent diabetic changes. Specific calcineurin-inhibitor nephrotoxicity was present in 93.3% of biopsies associated with thrombotic microangiopathy in 46.7% of cases. The identification of specific etiologies of progressive kidney disease in patients with CF after lung transplantation should permit more effective post-transplant care of these patients.

[Escitalopram and citalopram: the unexpected role of the R-enantiomer]. / Escitalopram et Citalopram: le rôle inattendu de l'énantiomère R.

Citalopram, a selective serotonin reuptake inhibitor, is composed of 2 enantiomers, R-citalopram and S-citalopram, 2 different non-superimposable mirror image forms of the same molecule. Separating these 2 enantiomers has enabled studying their individual properties. Citalopram's pharmacologic activity is centered on the S enantiomer's high affinity for the serotonin transporter which is twice as high as citalopram's and 30 to 40 times higher than R-citalopram. This leads to an inhibition of serotonin reuptake two times higher for escitalopram compared with citalopram and confirms that citalopram's pharmacologic activity is due to the S-enantiomer. Contrary to what might be expected, the effect of escitalopram (DCI of S-citalopram) is not superimposable on an equivalent dose of citalopram but is superior. Several hypotheses could explain this superiority. First, conversions of the S-enantiomer into the R-enantiomer may occur, but there is no reason why this phenomenon would happen more when both enantiomers are present than when escitalopram is alone. Furthermore, pharmacokinetic studies have shown that S or R configurations are stable in vivo. Second, a particular action of R-citalopram may influence the S-enantiomer's kinetic from intestinal absorption to blood-brain barrier. But concentrations of both enantiomers in the frontal cortex are the same. Therefore, R-citalopram does not interfere with escitalopram's kinetic. Finally, interactions may appear at the synaptic level. Results of experimentation, after in situ injection to the cortex level, confirm that an interaction between the 2 enantiomers takes place at that level. A direct negative interaction of R-citalopram on one or several effectors that create the antidepressive effect seems justified. This negative interaction has been studied in depth. Animal models have shown that the R-enantiomer has no antidepressive potential and when associated with escitalopram prohedonic effects disappear. Escitalopram is more powerful than citalopram in reducing anxiety but the presence of R-citalopram reduces the positive effects of escitalopram. We then may conclude that R-citalopram antagonizes the antidepressive effects of escitalopram and that its presence limits the therapeutic effect and reduces the speed of action of citalopram. The antagonism of escitalopram by R-citalopram was not expected and one hypothesis is that a direct interaction between the 2 enantiomers may occur on a particular site of the serotonin transporter. Results have shown that R-citalopram has a significant affinity only for the allosteric site of the transporter, which regulates the affinity of the ligand for the active site at the origin of serotonin reuptake inhibition. Unlike citalopram, escitalopram's pharmacologic action is not blocked by R-citalopram explaining its greater therapeutic efficacy and more rapid mode of action.

[Streptococcus pneumoniae cellulitis in a diabetic patient]. / Dermohypodermite cervicale à Streptococcus pneumoniae chez un patient diabétique.

Pneumococcal cellulitis is an uncommon infection. Head, neck, and trunk are usually affected in patients with hematological malignancies and lupus erythematosus. Limb cellulitis is frequently observed in patients with diabetes mellitus, drug abusers, or alcoholics. Patients present with septic shock most of the time. Surgical treatment is necessary in 50% of the cases. The outcome is usually favorable. We describe the case of a 72-year-old alcoholic patient with diabetes mellitus presenting with cellulitis and septic shock. Serotype 19 Streptococcus pneumoniae with abnormal susceptibility to penicillin (MIC: 0.75 mg/l) was isolated from cellulitis and in blood culture. The evolution was favorable after itavenous antibiotherapy combining ceftriaxone(DCI) (2 g/j), metronidazole(DCI) (1 g/j), and ciprofloxacin(DCI).

[A severe form of Chryseobacterium indologenes pneumonia in an immunocompetent patient]. / Une forme sévère de pneumopathie à Chryseobacterium indologenes chez l'immunocompétent.

We report a case of severe pneumonia due to Chryseobacterium indologenes in an immunocompetent patient. Chryseobacterium indologenes (formerly Flavobacterium indologenes) are saprophytic Gram-negative rods widely distributed in damp environment. Many sites of infection were described in the literature. These infections are always severe sometimes associated to multiple organ failure. The evolution is usually favorable with antibiotic treatment. Bacteria characteristically grow as yellow-pigmented colonies. They are naturally resistant to many antimicrobial agents. They are usually susceptible to piperacillin(DCI) alone or combined with tazobactam(DCI), ceftazidime(DCI), cefepime(DCI), fluoroquinolones(DCI), rifampin(DCI) and cotrimoxazole(DCI), but the in vitro susceptibility to these antibiotics should be systematically tested. Nevertheless, the optimum antibiotic treatment for Chryseobacterium-related infections remains to be established. In the case we report, the diagnosis was made according to the results of bronchial sample bacterial culture. This case report underlines the need for specific management of patients infected with this species.

5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization.

Antagonists at substance P receptors of the neurokinin 1 (NK1) type have been shown to represent a novel class of antidepressant drugs, with comparable clinical efficacy to the selective serotonin (5-HT) reuptake inhibitors (SSRIs). Because 5-HT(1A) receptors may be critically involved in the mechanisms of action of SSRIs, we examined whether these receptors could also be affected in a model of whole-life blockade of NK1 receptors, i.e. knock-out mice lacking the latter receptors (NK1-/-). 5-HT(1A) receptor labeling by the selective antagonist radioligand [(3)H]N-[2-[4-(2-methoxyphenyl)1-piperazinyl]-ethyl]-N-(2-pyridinyl)-cyclohexanecarboxamide (WAY 100635) and 5-HT(1A)-dependent [(35)S]GTP-gamma-S binding at the level of the dorsal raphe nucleus (DRN) in brain sections, as well as the concentration of 5-HT(1A) mRNA in the anterior raphe area were significantly reduced (-19 to -46%) in NK1-/- compared with NK1+/+ mice. Furthermore, a approximately 10-fold decrease in the potency of the 5-HT(1A) receptor agonist ipsapirone to inhibit the discharge of serotoninergic neurons in the dorsal raphe nucleus within brainstem slices, and reduced hypothermic response to 8-OH-DPAT, were noted in NK1-/- versus NK1+/+ mice. On the other hand, cortical 5-HT overflow caused by systemic injection of the SSRI paroxetine was four- to sixfold higher in freely moving NK1-/- mutants than in wild-type NK1+/+ mice. Accordingly, the constitutive lack of NK1 receptors appears to be associated with a downregulation/functional desensitization of 5-HT(1A) autoreceptors resembling that induced by chronic treatment with SSRI antidepressants. Double immunocytochemical labeling experiments suggest that such a heteroregulation of 5-HT(1A) autoreceptors in NK1-/- mutants does not reflect the existence of direct NK1-5-HT(1A) receptor interactions in normal mice.

Nephrotic syndrome, linear glomerular IgG deposits, and minimal glomerular changes. Report of a case.

A young adult patient had an unusual acute idiopathic nephrotic syndrome. This nephrotic syndrome was remarkable for (1) association with acute renal failure and hypertension, (2) finding of minimal glomerular changes with a linear fixation of the anti-human IgG conjugate along the glomerular capillary wall without demonstrable antiglomerular basement membrane antibodies, and (3) complete recovery, including disappearance of the linear staining, after treatment with prednisone, cyclophosphamide, and plasmapheresis.

Long-term blood pressure changes in renal homotransplantation.

Long-term blood pressure changes were studied in 50 patients who had undergone renal homotransplantation. Excluded were those subjects with arterial stenosis of the transplanted kidney, acute or rapidly progressive rejection, or recurrent glomerulonephritis, as well as those retaining their own diseased kidney(s). The blood pressure after the end of the first year was stable and, therefore, was utilized as the reference blood pressure for this study. One year after transplantation, hypertension was observed in 20% of the patients. Mean blood pressure was positively correlated with age (P less than .01), body weight (P less than .001), and serum creatinine level (P less than .001), and negatively correlated with maintenance dose of prednisone (P less than .01). A higher incidence of hypertension was observed in cadaver kidney transplantation than in living related-donor transplantation. The study minimizes the role of glucocorticoids and emphasizes the role of renal factors in the mechanism of the long-term blood pressure changes.

Impact of kefir derived Lactobacillus kefiri on the mucosal immune response and gut microbiota.

The evaluation of the impact of probiotics on host health could help to understand how they can be used in the prevention of diseases. On the basis of our previous studies and in vitro assays on PBMC and Caco-2 ccl20:luc reporter system presented in this work, the strain Lactobacillus kefiri CIDCA 8348 was selected and administrated to healthy Swiss mice daily for 21 days. The probiotic treatment increased IgA in feces and reduced expression of proinflammatory mediators in Peyer Patches and mesenteric lymph nodes, where it also increased IL-10. In ileum IL-10, CXCL-1 and mucin 6 genes were upregulated; meanwhile in colon mucin 4 was induced whereas IFN-γ, GM-CSF, and IL-1ß genes were downregulated. Moreover, ileum and colon explants showed the anti-inflammatory effect of L. kefiri since the LPS-induced increment of IL-6 and GM-CSF levels in control mice was significantly attenuated in L. kefiri treated mice. Regarding fecal microbiota, DGGE profiles allowed differentiation of experimental groups in two separated clusters. Quantitative PCR analysis of different bacterial groups revealed only significant changes in Lactobacillus population. In conclusion, L. kefiri is a good candidate to be used in gut inflammatory disorders.

Simultaneous effects of local dexfenfluramine application on extracellular glutamate and serotonin levels in rat frontal cortex: a reverse microdialysis study.

We examined the effects of local perfusion by reverse dialysis of various doses of dexfenfluramine (D-fen; in mM: 2.4, 12, and 24) simultaneously on serotonin (5-HT; [5-HT]ext) and glutamate (Glu; [Glu]ext) extracellular levels in the frontal cortex of awake rats. D-fen induced a dose-dependent increase in both [5-HT]ext and [Glu]ext, the latter being Ca2+ -dependent and TTX-sensitive, while the former is not. Pretreatment with either the neurotoxin p-chloroamphetamine or the 5-HT uptake blocker fluoxetine, markedly reduced the effects of D-fen on [5-HT]ext and [Glu]ext compared to controls. This indicates that intact 5-HT nerve terminals may be required for D-fen to enter into neurones to release 5-HT by reversal of the 5-HT transporter, which then increases frontocortical [Glu]ext. Pretreatment with the Glu uptake blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM), significantly reduced by 40% the effect of D-fen's on [Glu]ext suggesting that Glu uptake sites are partially involved in this effect. These results strongly suggest that intracortical application, by reverse dialysis, of a high dose of D-fen increases frontocortical [Glu]ext by a dual mechanism of action: (1) by stimulating 5-HT release (a major indirect effect) that, in turn, facilitates the release of neuronal Glu; (2) by reversal of the glutamate transporter (a minor direct effect being Ca2+ -independent and TTX-insensitive).

Fenfluramine and brain transmitters in the obese Zucker rat.

Genetically obese Zucker rats and their lean litter mates were treated for 5 days with fenfluramine. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) and their metabolism were assayed in the hypothalamus, striatum, medulla-oblongata pons and remainder of the brain. Fenfluramine induced a slight increase in the level of NE in the hypothalamus in lean rats and a marked decrease in obese rats. No change in the synthesis of NE was found. Fenfluramine had no effect on the level and metabolism of DA. The levels of 5-HT were decreased by fenfluramine in obese and lean rats, and the metabolism was increased. The levels of GABA were not changed by fenfluramine. Synthesis of GABA was increased in the remainder of the brain of obese and lean rats. These data suggest that fenfluramine acts on 5-HT systems in both obese and lean rats and are consistent with reports of the pharmacological effects of fenfluramine.

Cholecystokinin and bombesin in vagotomized or intact lean and obese rats: effects on neurotransmitters in brain.

Cholecystokinin (CCK) and Bombesin (BBS) are two neuropeptides which induce changes in monoamines in the brain after peripheral administration. A vagal mediation of these effects was investigated since the satiety responses to both peptides are affected differently by vagotomy. This work was performed on genetically obese and lean Zucker rats and on "cafeteria-fed" and lean Sprague-Dawley rats as the effects of the peptides are dissimilar in these different groups. Vagotomy either inhibited or potentiated the peptide-induced effects, or created new variations. With CCK, the inhibition occurred mainly in the serotonergic system and in the Zucker strain, while new effects appeared in the dopaminergic system of lean rats of both strains. With bombesin, vagotomy inhibited the effects in the dopaminergic system in all lean rats, while new effects were observed in the serotonergic system in the Zucker strain. These data enable the differentiation of the mechanisms of action of both peptides and their selective effects, according to the strain of rat and the presence or absence of obesity.

Antithrombin III and heparin cofactor II in patients with chronic renal failure undergoing regular hemodialysis.

Heparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean +/- 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p less than 0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p less than 0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p less than 0.01) whereas HC II increased slightly but significantly (p less than 0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.

Supportive treatment improves survival in multivisceral cholesterol crystal embolism.

Disseminated cholesterol crystal embolism (CCE) is a devastating complication of atherosclerosis that is often considered beyond therapeutic resources. We designed and implemented a treatment protocol based on an analysis of the main causes of death in disseminated CCE with renal involvement. From 1985 to 1996, we applied this protocol in 67 consecutive atherosclerotic patients admitted to our renal intensive care unit for acute renal failure (serum creatinine level, 6 +/- 2.5 mg/dL) accompanied by signs and symptoms of CCE. The other principal clinical features in these patients were cardiac failure with pulmonary edema (61%), gastrointestinal ischemia (33%), cutaneous ischemia (90%), and retinal cholesterol embolism (22%). Disseminated CCE followed one or several precipitating factors, including angiographic procedure(s) (85%), anticoagulant treatment (76%), and cardiovascular surgery (33%). Our treatment schedule systematically addressed the identified causes of death in these patients. (1) To avoid CCE recurrence, any form of anticoagulant treatment was withdrawn, and aortic catheterization and surgery were proscribed. (2) To treat or prevent cardiac failure, a high-dose vasodilator regimen was instituted, including angiotensin-converting enzyme (ACE) inhibitors. In case of cardiac failure refractory to vasodilators, loop diuretics were added and, if necessary, overhydration was corrected by ultrafiltration/hemodialysis (11 patients). (3) To avoid cachexia, severe metabolic disorders were treated by hemodialysis (41 patients), and special attention was given to providing enteral or parenteral nutritional support. Patients with declining general status and laboratory evidence of inflammation, as well as those with new episodes of CCE, were treated with corticosteroids. Statistical analysis found a significant correlation between the requirement for hemodialysis and previous anticoagulation, degree of renal insufficiency, and severity of cardiac failure. Conversely, there was no correlation between requirement for hemodialysis and ACE inhibitor treatment or presence of atherosclerotic renal artery stenosis/thrombosis. The inhospital mortality rate was 16%. There were no clinical or laboratory elements found on admission that were predictive of inhospital mortality. Among survivors, 32% had to remain on maintenance hemodialysis therapy for irreversible chronic renal failure. Including initial hospitalization, the 1-year survival rate was 87%, which compares favorably with reports in the literature indicating a first-year mortality rate of 64% to 81%. Overall follow-up was 19 +/- 20 months, ranging from 1 to 74 months. The 4-year survival rate was 52%. We conclude that an intensive-care, specific-treatment schedule reduces mortality in multivisceral cholesterol embolism.

Albumin binding and brain uptake of 6-fluoro-DL-tryptophan: competition with L-tryptophan.

We investigated potential competition between L-tryptophan (TRP) and 6-fluoro-DL-tryptophan (6-F-TRP) for binding to albumin and for passage through the blood-brain barrier (BBB). In experiments based on equilibrium dialysis, albumin (600 microM) bound about 80% of TRP and 50% of 6-F-TRP with affinity constants (Ka) of 3.7 +/- 0.04 x 10(4) and 0.62 +/- 0.01 x 10(4) M-1, respectively. Competitive inhibition was assessed as the decrease in the apparent Ka (K' a) of TRP in the presence of 6-F-TRP, with no modification of the N value. Competition between TRP, 6-F-TRP and L-valine (VAL) for passage across the BBB was demonstrated using two approaches. When administered concomitantly with TRP or 6-F-TRP to rats, VAL decreased brain uptake of TRP and 6-F-TRP and reversed their action on serotonin. In Oldendorf's model, 6-F-TRP and VAL decreased the brain uptake of TRP.

Metabolism of 6-fluoro-DL-tryptophan and its specific effects on the rat brain serotoninergic pathway.

We administered 6-fluoro-DL-tryptophan (6F-Trp) to rats (50-200 mg/kg i.p.) and evaluated its neurochemical effects on central catechole and indole compounds; we also determined the time course of its action, together with its metabolism and kinetics in four rat brain areas. Neither norepinephrine nor dopamine and its major metabolites were affected by 6F-Trp. With regard to serotonin (5-HT), 6F-Trp induced a transient depletion in all the brain areas studied, with a maximum of about 60-65% obtained between 1 and 3 hr depending on the dose administered. After 6 hr, 5-HT levels generally returned to control values. 5-Hydroxyindolacetic acid (5-HIAA) levels were also reduced 3 hr after administration (-40 to -60%). A large dose-dependent increase in tryptophan (Trp) was observed in the four brain areas, possibly because of an inhibition of Trp incorporation into protein, as suggested by experiments with mouse neuroblastoma cells. The brain elimination half-life of 6F-Trp was estimated at 0.5-1 hr. Regarding 6F-Trp metabolism, three new compounds were detected in all four brain areas after 6F-Trp administration. They were identified by means of liquid chromatography with electrochemical detection and/or radioenzymology, in comparison with fluorinated standards, or after NSD 1015 or pargyline coadministration with 6F-Trp. The first two 6F-Trp metabolites detected were probably 6-fluoro-5-hydroxytryptophan and 6-fluoro-5-HIAA. The third, identified and quantified by means of the two analytical methods, was 6-fluoro-5-HT (6F-5-HT). These findings suggest that 6F-Trp could be used as the in vivo precursor of 6F-5-HT with a view to tracing neuronal serotoninergic pools, as has already been done with platelets.